Durable Phase 2 Melanoma Signal Faces Phase 3, Manufacturing and Payer Test

Moderna's Q3 Revenue Boosted by Global COVID Vaccine Uptake

Moderna reported a 29% increase in Q3 revenue to $1.3 billion, primarily driven by stable global sales of its COVID-19 vaccines, mNEXSPIKE and Spikevax. The company also saw strong performance from its broader vaccine portfolio, including mRESVIA for RSV and mFLUSIVA for flu, contributing to $1.27 billion in total vaccine sales. Moderna raised its full-year revenue guidance to a 15-25% increase. Looking ahead, Moderna is preparing for a significant entry into the oncology market in 2027 with its personalized cancer vaccine, intismeran autogene, partnered with Merck, which showed a 42% reduction in recurrence or death risk in melanoma patients.

• Moderna's third-quarter revenue surged by 29% to $1.3 billion, surpassing $1 billion from the previous year, with year-to-date revenue reaching $1.8 billion. This growth was largely attributed to robust global uptake of its COVID-19 vaccines, mNEXSPIKE and Spikevax, leading to total vaccine sales of $1.27 billion, significantly exceeding analyst consensus.
• Beyond COVID-19, Moderna's vaccine sales included contributions from mRESVIA (RSV) and mFLUSIVA (flu), which became available in some global markets. The company raised its full-year revenue expectations to a 15-25% increase, confident in continued growth from flu vaccine launches and major partnerships in Europe and Latin America, despite a setback with the norovirus vaccine mRNA-1403.
• Moderna is poised to enter the oncology market in 2027 with its personalized cancer vaccine, intismeran autogene, developed in partnership with Merck. This vaccine demonstrated promising results in melanoma patients, reducing the risk of recurrence or death by 42% when combined with Keytruda in the Phase 3 INTerpath-001 trial. The partners are also exploring its potential in renal cell carcinoma, with a Phase 2 readout anticipated.

Evolving COVID-19 Treatment Landscape and Moderna's Position

Hospitalized severe COVID-19 was initially addressed with direct antiviral and antibody-based strategies. A retrospective study among consecutive patients admitted to the Infectious Disease ward of the University of Naples (Italy) Hospital from August 1, 2021 to November 30, 2021 described 14 patients who received the combination of casirivimab/imdevimab and remdesivir, including five males and nine females with a median age of 54 years, with no adverse drug reaction observed and all patients except one improved clinical condition and respiratory parameters within seven days following the therapy. The RES-Q-HR study was designed as a 4-arm (parallel group), multicenter, randomized (2:2:1:1 ratio), partly double-blind, controlled trial to evaluate convalescent plasma (CP) or camostat mesylate with control or placebo in adult patients diagnosed with SARS-CoV-2 infection and high risk for progression, randomizing n = 994 participants to convalescent plasma (CP), n = 331 to camostat mesylate, n = 166 to standard of care (SoC), and n = 166 to placebo matching camostat mesylate, with the primary endpoint defined as the cumulative number of individuals who progress to or beyond category 4b on the modified WHO COVID-19 ordinal scale within 28 days after randomization. In immunocompromised patients persistently positive for SARS-CoV-2 viraemia following anti-Spike monoclonal antibody therapy, 33 out of 47 patients (70.2%) achieved SARS-CoV-2 clearance following CCP transfusion, with a mean of 2.7 CCP units administered, and total CCP volume transfused was positively associated with SARS-CoV-2 clearance in logistic regression.

Host protease and hyperinflammation-directed approaches were evaluated in randomized and prospective studies. A multicentre, double-blind, randomized trial in four Spanish hospitals comparing standard treatment versus standard treatment + aprotinin for patients with COVID-19 between 20 May 2020 and 20 October 2021 reported treatment time 2 days lower in the aprotinin group (p = .002), length of hospital admission 5 days shorter in the aprotinin group (p = .003), and incidence of discharge 2.19 times higher (HR: 2.188 [1.182-4.047]) in the aprotinin group than in the placebo group (p = .013). Cohort 1 of a randomized, placebo-controlled trial of the BTK inhibitor zanubrutinib randomized adults requiring hospitalization without mechanical ventilation 1:1 to zanubrutinib 320 mg once daily or placebo, with 63 patients receiving zanubrutinib (n=30) or placebo (n=33) and median treatment duration of 8.5 and 7.0 days, respectively, while cohort 2 enrolled those on mechanical ventilation ≤24 hours to zanubrutinib 320 mg once daily with median treatment duration in cohort 2 (n=4) of 13 days; respiratory failure-free survival and the estimated rates of not returning to breathing room air by day 28 were not significantly different between treatments, serological response to coronavirus disease 2019 (COVID-19) was not impacted by zanubrutinib, and single-cell transcriptome analysis showed significant downregulation of inflammatory mediators (IL-6, IL-8, macrophage colony-stimulating factor, macrophage inflammatory protein-1α, IL-1β) and signaling pathways (JAK1, STAT3, TYK2). A non-randomized prospective phase II multi-center study treated 16 SARS-CoV-2 infected patients requiring invasive mechanical ventilation for ARDS with ruxolitinib in addition to standard treatment, with 13 patients surviving at least the first 28 days on treatment, and immediate start of ruxolitinib after deterioration was associated with improved outcome, as was a lymphocyte-to-neutrophils ratio above 0.07.

Corticosteroid comparisons further refined standard care for respiratory failure. A retrospective clinical study reviewing files of 500 hospitalized COVID-19 patients found no significant difference in most disease severity-associated markers between dexamethasone and methylprednisolone groups, while lower mortality rates and shortened hospital stays were significantly associated with dexamethasone, especially in critical patient groups. A meta-analysis of four studies comparing low-dose versus high-dose dexamethasone found no significant difference in ICU admission (risk ratio (RR): 0.72, 95% confidence interval (CI): 0.41-1.28, p-value: 0.27), length of stay in ICU in days (mean difference (MD): -0.05, 95%CI: -3.96-3.87, p-value: 0.98), length of hospital stay in days (MD: -0.94, 95%CI: -1.94-0.06, p-value: 0.07), need of mechanical ventilation (RR: 0.72, 95%CI: 0.36-1.48, p-value: 0.38), and 28-day mortality (RR: 0.90, 95% CI: 0.50-1.64, p-value: 0.74). In patients receiving B-cell-depleting therapies who contracted COVID-19 within a year from the last BCDT, a retrospective review of 64 included patients treated with rituximab (55%), obinutuzumab (33%), ocrelizumab (11%) and ofatumumab (1%) reported seven deceased patients with three died from COVID-19, all three elderly males with multiple comorbidities treated inpatient for severe COVID-19, and all deceased and hospitalized patients had an underlying hematological malignancy.

Addressing Unmet Needs in COVID-19 Prevention and Treatment

Recent literature from 2023 to 2026 focuses COVID-19 prevention and treatment efforts on populations with elevated risk of severe outcomes and persistent disparities despite vaccination and therapeutic advances. Long COVID rehabilitation and tailored vaccine and antiviral strategies remain central themes across age groups and care settings.

• Older adults and nursing home residents: Nursing home residents remain at high risk due to age, comorbidities, and congregate exposure, with up-to-date vaccine effectiveness (versus not being up to date) against laboratory-confirmed SARS-CoV-2 infection of 31.2% (95% CI = 29.1%-33.2%) during November 20, 2022-January 8, 2023. In old adults (mean/median age of 60 or older) with long COVID, rehabilitation interventions significantly improved 6-minute walking test (MD = 15.77 metres (m), 95% CI = 5.40, 26.13, P < 0.01), 30-second sit-to-stand test, all aspects of quality of life, independence in activities of daily living, fatigue, depression and anxiety, while improvement of hand grip strength and pulmonary function was not statistically significant (P > 0.05).

• Immunocompromised individuals including lung transplant recipients: Populations include adults and children with hematologic malignancy, solid organ or hematopoietic cell transplantation, autoimmune disease on immunosuppressants, HIV with severe immunosuppression, primary immunodeficiency, and chimeric antigen receptor T-cell therapy (CAR-T). COVID-19 vaccination was associated with reduced hospitalization (33-56% effectiveness), critical illness, mortality, and COVID-19-related outpatient or emergency care visits, with rare serious adverse events. Among 195 lung transplant recipients diagnosed with COVID-19 between March 2020 and August 2022, 113 (58.5%) were hospitalized and 47 (24.1%) died, with remdesivir and molnupiravir reducing risk of hospitalization and monoclonal antibody therapy reducing risk of ICU admission, intubation, and death, while 2023-2024 XBB vaccine uptake was only 21% in California and 6% in Louisiana.

• Children aged ≥6 months and pregnant persons: Vaccines authorized for use in children include two monovalent mRNA vaccines (≥6 months old) and one monovalent protein subunit adjuvant vaccine (adolescents only), with Omicron-specific mRNA bivalent boosters authorized for children ≥6 months old and sufficient data to recommend vaccination for children ≥6 months of age. Among pregnant people aged 18 to 45 years during June 2022 to August 2023, vaccine effectiveness against medically attended COVID-19 with COVID-19-like illness was 52% (95% CI, 29%-67%) when doses were received during pregnancy, 28% (95% CI, 11%-42%) when received <6 months prior to pregnancy, and 6% (95% CI, -11% to 21%) when received ≥6 months prior to pregnancy.

• Rural versus urban communities: In 3,018,646 patients including 506,204 rural residents from 2021 to 2023, rural dwellers were older, had more comorbidities, and were less vaccinated, with higher hospitalization odds in urban-adjacent rural and nonurban-adjacent rural (aOR 1.07 [1.05-1.08] and 1.06 [1.03-1.08]) and greater inpatient death hazard (aHR 1.30 [1.26-1.35] and 1.37 [1.30-1.45]). Nirmatrelvir/ritonavir and molnupiravir better protected rural residents against hospitalization, but dexamethasone post-ventilation was effective only in urban areas.

• Long COVID burden and rehabilitation needs: Globally in 2020 and 2021, 144.7 million (95% uncertainty interval [UI] 54.8-312.9) people suffered from any of three symptom clusters, corresponding to 3.69% (1.38-7.96) of all infections, with fatigue, respiratory, and cognitive clusters in 51.0% (16.9-92.4), 60.4% (18.9-89.1), and 35.4% (9.4-75.1) of long COVID cases, respectively, and 15.1% (10.3-21.1) continuing to experience symptoms at twelve months. Dyspnea, chronic cough, and fatigue are the most commonly reported symptoms in the first 6 months after infection, but cognitive impairment and psychological symptoms may persist beyond this time, with early management starting with comprehensive evaluation and identification of red flags and exercise-based therapy including telerehabilitation.